+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-42102 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of SCF-FBXL17-BACH1BTB E3 ligase complex | |||||||||
Map data | The composite EM map of SCF(CUL1RBX1SKP1)-FBXL17-BACH1BTB by combining focused refined FBXL17-BACH1BTB (filtered by DeepEMhancer) and global EM map. | |||||||||
Sample |
| |||||||||
Keywords | SCF / FBXL17 / BACH1 / F-box protein / E3 ligase / LIGASE | |||||||||
Function / homology | Function and homology information Regulation of HMOX1 expression and activity / Parkin-FBXW7-Cul1 ubiquitin ligase complex / F-box domain binding / PcG protein complex / ligand-activated transcription factor activity / cullin-RING ubiquitin ligase complex / regulation of smoothened signaling pathway / positive regulation of ubiquitin protein ligase activity / Cul7-RING ubiquitin ligase complex / maintenance of protein location in nucleus ...Regulation of HMOX1 expression and activity / Parkin-FBXW7-Cul1 ubiquitin ligase complex / F-box domain binding / PcG protein complex / ligand-activated transcription factor activity / cullin-RING ubiquitin ligase complex / regulation of smoothened signaling pathway / positive regulation of ubiquitin protein ligase activity / Cul7-RING ubiquitin ligase complex / maintenance of protein location in nucleus / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / regulation of metabolic process / neural crest cell differentiation / SCF ubiquitin ligase complex / NFE2L2 regulating anti-oxidant/detoxification enzymes / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / ubiquitin ligase complex scaffold activity / protein quality control for misfolded or incompletely synthesized proteins / entrainment of circadian clock by photoperiod / Prolactin receptor signaling / protein monoubiquitination / cullin family protein binding / ubiquitin-like ligase-substrate adaptor activity / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / intrinsic apoptotic signaling pathway / Regulation of BACH1 activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / molecular function activator activity / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / Vpu mediated degradation of CD4 / animal organ morphogenesis / Dectin-1 mediated noncanonical NF-kB signaling / Iron uptake and transport / Activation of NF-kappaB in B cells / Degradation of GLI1 by the proteasome / Negative regulation of NOTCH4 signaling / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Heme signaling / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / Degradation of beta-catenin by the destruction complex / NOTCH1 Intracellular Domain Regulates Transcription / CLEC7A (Dectin-1) signaling / DNA-binding transcription repressor activity, RNA polymerase II-specific / SCF(Skp2)-mediated degradation of p27/p21 / beta-catenin binding / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / FCERI mediated NF-kB activation / Interleukin-1 signaling / Orc1 removal from chromatin / protein polyubiquitination / RNA polymerase II transcription regulator complex / G1/S transition of mitotic cell cycle / Regulation of RUNX2 expression and activity / Cyclin D associated events in G1 / Regulation of PLK1 Activity at G2/M Transition / Circadian Clock / Antigen processing: Ubiquitination & Proteasome degradation / Downstream TCR signaling / Neddylation / nervous system development / protein-macromolecule adaptor activity / DNA-binding transcription activator activity, RNA polymerase II-specific / positive regulation of canonical NF-kappaB signal transduction / proteasome-mediated ubiquitin-dependent protein catabolic process / cell population proliferation / DNA-binding transcription factor activity, RNA polymerase II-specific / protein ubiquitination / chromatin remodeling / DNA-binding transcription factor activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / protein domain specific binding / DNA repair / centrosome / ubiquitin protein ligase binding / heme binding / regulation of DNA-templated transcription / chromatin / regulation of transcription by RNA polymerase II / negative regulation of transcription by RNA polymerase II / nucleoplasm / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Shi H / Cao S | |||||||||
Funding support | United States, 1 items
| |||||||||
Citation | Journal: bioRxiv / Year: 2024 Title: Distinct Perception Mechanisms of BACH1 Quaternary Structure Degrons by Two F-box Proteins under Oxidative Stress. Authors: Shiyun Cao / Huigang Shi / Sheena Faye Garcia / Yuki Kito / Hui Shi / Hailey V Goldberg / Jackeline Ponce / Beatrix Ueberheide / Luca Lignitto / Michele Pagano / Ning Zheng / Abstract: The transcription factor BACH1 regulates heme homeostasis and oxidative stress responses and promotes cancer metastasis upon aberrant accumulation. Its stability is controlled by two F-box protein ...The transcription factor BACH1 regulates heme homeostasis and oxidative stress responses and promotes cancer metastasis upon aberrant accumulation. Its stability is controlled by two F-box protein ubiquitin ligases, FBXO22 and FBXL17. Here we show that the homodimeric BTB domain of BACH1 functions as a previously undescribed quaternary structure degron, which is deciphered by the two F-box proteins via distinct mechanisms. After BACH1 is released from chromatin by heme, FBXO22 asymmetrically recognizes a cross-protomer interface of the intact BACH1 BTB dimer, which is otherwise masked by the co-repressor NCOR1. If the BACH1 BTB dimer escapes the surveillance by FBXO22 due to oxidative modifications, its quaternary structure integrity is probed by a pair of FBXL17, which simultaneously engage and remodel the two BTB protomers into E3-bound monomers for ubiquitination. By unveiling the multifaceted regulatory mechanisms of BACH1 stability, our studies highlight the abilities of ubiquitin ligases to decode high-order protein assemblies and reveal therapeutic opportunities to block cancer invasion via compound-induced BACH1 destabilization. | |||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_42102.map.gz | 95.4 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-42102-v30.xml emd-42102.xml | 29.4 KB 29.4 KB | Display Display | EMDB header |
Images | emd_42102.png | 115.7 KB | ||
Masks | emd_42102_msk_1.map | 103 MB | Mask map | |
Filedesc metadata | emd-42102.cif.gz | 7.3 KB | ||
Others | emd_42102_additional_1.map.gz emd_42102_additional_2.map.gz emd_42102_additional_3.map.gz emd_42102_additional_4.map.gz emd_42102_half_map_1.map.gz emd_42102_half_map_2.map.gz | 95 MB 95.4 MB 95.2 MB 85.5 MB 95.3 MB 95.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-42102 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-42102 | HTTPS FTP |
-Validation report
Summary document | emd_42102_validation.pdf.gz | 930.1 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_42102_full_validation.pdf.gz | 929.7 KB | Display | |
Data in XML | emd_42102_validation.xml.gz | 13.5 KB | Display | |
Data in CIF | emd_42102_validation.cif.gz | 15.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-42102 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-42102 | HTTPS FTP |
-Related structure data
Related structure data | 8ubtMC 8ua3C 8ua6C 8uahC 8ubuC 8ubvC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_42102.map.gz / Format: CCP4 / Size: 110.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | The composite EM map of SCF(CUL1RBX1SKP1)-FBXL17-BACH1BTB by combining focused refined FBXL17-BACH1BTB (filtered by DeepEMhancer) and global EM map. | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. generated in cubic-lattice coordinate | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.743 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | emd_42102_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: The composite EM map of SCF(CUL1RBX1SKP1)-FBXL17-BACH1BTB by combining...
File | emd_42102_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | The composite EM map of SCF(CUL1RBX1SKP1)-FBXL17-BACH1BTB by combining focused refined FBXL17-BACH1BTB and global EM map. | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: The global EM map of SCF(CUL1RBX1SKP1)-FBXL17-BACH1BTB generated by...
File | emd_42102_additional_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | The global EM map of SCF(CUL1RBX1SKP1)-FBXL17-BACH1BTB generated by Non-uniform refinement in cryoSPARC. | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: The local refinement EM map of SCF(CUL1RBX1SKP1)-FBXL17-BACH1BTB with...
File | emd_42102_additional_3.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | The local refinement EM map of SCF(CUL1RBX1SKP1)-FBXL17-BACH1BTB with a mask including the density of Fbxl17-BACH1BTB. | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: The DeepEMhancer filtered local refinement EM map of...
File | emd_42102_additional_4.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | The DeepEMhancer filtered local refinement EM map of SCF(CUL1RBX1SKP1)-FBXL17-BACH1BTB with a mask including the density of Fbxl17-BACH1BTB. | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: The half map of SCF-FBXL17-BACH1BTB complex generated by...
File | emd_42102_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | The half map of SCF-FBXL17-BACH1BTB complex generated by Non-uniform reifnement in cryoSPARC. | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: The half map of SCF-FBXL17-BACH1BTB complex generated by...
File | emd_42102_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | The half map of SCF-FBXL17-BACH1BTB complex generated by Non-uniform reifnement in cryoSPARC. | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : The SCF-F-box protein with BACH1 BTB Domain, SCF-BFXL17-BACH1BTB
Entire | Name: The SCF-F-box protein with BACH1 BTB Domain, SCF-BFXL17-BACH1BTB |
---|---|
Components |
|
-Supramolecule #1: The SCF-F-box protein with BACH1 BTB Domain, SCF-BFXL17-BACH1BTB
Supramolecule | Name: The SCF-F-box protein with BACH1 BTB Domain, SCF-BFXL17-BACH1BTB type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Cullin-1
Macromolecule | Name: Cullin-1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 88.501945 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: KQIGLDQIWD DLRAGIQQVY TRQSMAKSRY MELYTHVYNY CTSVHQSNQA RGAGVPPSKS KKGQTPGGAQ FVGLELYKRL KEFLKNYLT NLLKDGEDLM DESVLKFYTQ QWEDYRFSSK VLNGICAYLN RHWVRRECDE GRKGIYEIYS LALVTWRDCL F RPLNKQVT ...String: KQIGLDQIWD DLRAGIQQVY TRQSMAKSRY MELYTHVYNY CTSVHQSNQA RGAGVPPSKS KKGQTPGGAQ FVGLELYKRL KEFLKNYLT NLLKDGEDLM DESVLKFYTQ QWEDYRFSSK VLNGICAYLN RHWVRRECDE GRKGIYEIYS LALVTWRDCL F RPLNKQVT NAVLKLIEKE RNGETINTRL ISGVVQSYVE LGLNEDDAFA KGPTLTVYKE SFESQFLADT ERFYTRESTE FL QQNPVTE YMKKAEARLL EEQRRVQVYL HESTQDELAR KCEQVLIEKH LEIFHTEFQN LLDADKNEDL GRMYNLVSRI QDG LGELKK LLETHIHNQG LAAIEKCGEA ALNDPKMYVQ TVLDVHKKYN ALVMSAFNND AGFVAALDKA CGRFINNNAV TKMA QSSSK SPELLARYCD SLLKKSSKNP EEAELEDTLN QVMVVFKYIE DKDVFQKFYA KMLAKRLVHQ NSASDDAEAS MISKL KQAC GFEYTSKLQR MFQDIGVSKD LNEQFKKHLT NSEPLDLDFS IQVLSSGSWP FQQSCTFALP SELERSYQRF TAFYAS RHS GRKLTWLYQL SKGELVTNCF KNRYTLQAST FQMAILLQYN TEDAYTVQQL TDSTQIKMDI LAQVLQILLK SKLLVLE DE NANVDEVELK PDTLIKLYLG YKNKKLRVNI NVPMKTEQKQ EQETTHKNIE EDRKLLIQAA IVRIMKMRKV LKHQQLLG E VLTQLSSRFK PRVPVIKKCI DILIEKEYLE RVDGEKDTYS YLA UniProtKB: Cullin-1 |
-Macromolecule #2: S-phase kinase-associated protein 1
Macromolecule | Name: S-phase kinase-associated protein 1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 18.679965 KDa |
Recombinant expression | Organism: Escherichia coli BL21 (bacteria) |
Sequence | String: MPSIKLQSSD GEIFEVDVEI AKQSVTIKTM LEDLGMDDEG DDDPVPLPNV NAAILKKVIQ WCTHHKDDPP PPEDDENKEK RTDDIPVWD QEFLKVDQGT LFELILAANY LDIKGLLDVT CKTVANMIKG KTPEEIRKTF NIKNDFTEEE EAQVRKENQW C EEK UniProtKB: S-phase kinase-associated protein 1 |
-Macromolecule #3: F-box/LRR-repeat protein 17
Macromolecule | Name: F-box/LRR-repeat protein 17 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 44.505512 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: CHREPPPETP DINQLPPSIL LKIFSNLSLD ERCLSASLVC KYWRDLCLDF QFWKQLDLSS RQQVTDELLE KIASRSQNII EINISDCRS MSDNGVCVLA FKCPGLLRYT AYRCKQLSDT SIIAVASHCP LLQKVHVGNQ DKLTDEGLKQ LGSKCRELKD I HFGQCYKI ...String: CHREPPPETP DINQLPPSIL LKIFSNLSLD ERCLSASLVC KYWRDLCLDF QFWKQLDLSS RQQVTDELLE KIASRSQNII EINISDCRS MSDNGVCVLA FKCPGLLRYT AYRCKQLSDT SIIAVASHCP LLQKVHVGNQ DKLTDEGLKQ LGSKCRELKD I HFGQCYKI SDEGMIVIAK GCLKLQRIYM QENKLVTDQS VKAFAEHCPE LQYVGFMGCS VTSKGVIHLT KLRNLSSLDL RH ITELDNE TVMEIVKRCK NLSSLNLCLN WIINDRCVEV IAKEGQNLKE LYLVSCKITD YALIAIGRYS MTIETVDVGW CKE ITDQGA TLIAQSSKSL RYLGLMRCDK VNEVTVEQLV QQYPHITFST VLQDCKRTLE RAYQMGWTPN MSAASS UniProtKB: F-box/LRR-repeat protein 17 |
-Macromolecule #4: Transcription regulator protein BACH1
Macromolecule | Name: Transcription regulator protein BACH1 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.839761 KDa |
Recombinant expression | Organism: Escherichia coli BL21 (bacteria) |
Sequence | String: SVFAYESSVH STNVLLSLND QRKKDVLCDV TIFVEGQRFR AHRSVLAACS SYFHSRIVGQ ADGELNITLP EEVTVKGFEP LIQFAYTAK LILSKENVDE VCKCVEFLSV HNIEESCFQF LKF UniProtKB: Transcription regulator protein BACH1 |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
---|---|
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | TFS KRIOS |
---|---|
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 25.0 µm / Nominal defocus min: 5.0 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |